tbuckley/cabot-search huggingface dataset:
The results of genetic analysis and clinical outcomes after stent deployment in adult patients with isolated peripheral pulmonary artery stenosis
Authors: Misaki Kanezawa, Hiroto Shimokawahara, Masahiro Tsuji, Kazuki Suruga, Ayane Miyagi, Minako Marunaka, Takashi Mukai, Takahisa Kawaguchi, Ta-Yu Yang, Izumi Yamaguchi, Masao Nagasaki, Fumihiko Matsuda, Hiromi Matsubara
Journal: European Respiratory Journal (2023)

Peripheral pulmonary arterial stenosis (PPAS) is commonly observed in pediatric patients with associated congenital heart disease or systemic congenital syndromes, such as tetralogy of Fallot and Williams syndrome [1]. Meanwhile, isolated PPAS without other structural heart disease or systemic congenital syndromes is primarily reported in adulthood [2]. Recent genetic analyses have revealed that four cases of isolated PPAS in adulthood were homozygous for the ring finger protein 213 (RNF213) p.Arg4810Lys variant (also referred to as G to A alteration of rs112735431 and NM_001256071.3:c.14429G>A) [3]. RNF213 p.Arg4810Lys is a genetic determinant in Moyamoya disease (MMD) in East Asians [4]. This genetic variant is unique to East Asians and is reported to have a frequency of approximately 0.8% in the general Japanese population [5, 6]. However, its prevalence in adult patients with isolated PPAS remains unknown. Footnotes This manuscript has recently been accepted for publication in the European Respiratory Journal . It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article. Conflict of interest: Dr. Shimokawahara received lecture fees from Bayer Yakuhin and Nippon Shinyaku and research funding from Bayer Yakuhin. Conflict of interest: Dr. Matsubara has received lecture fees from Bayer, Nippon Shinyaku, Janssen, Mochida Yakuhin, Nipro, and Kaneka Medix. Conflict of interest: Dr. Matsubara is involved in collaborative research with Nippon Shinyaku. Conflict of interest: The other authors have no conflicts of interest to disclose.
The impact of outpatient<i>versus</i>inpatient management on health-related quality of life outcomes for patients with malignant pleural effusion: the OPTIMUM randomised clinical trial
Authors: Parthipan Sivakumar, Deirdre B. Fitzgerald, Hugh Ip, Deepak Rao, Alex West, Farinaz Noorzad, Deirdre Wallace, Mohamed Haris, Benjamin Prudon, Gihan Hettiarachchi, Deepak Jayaram, James Goldring, Nick Maskell, Jayne Holme, Neel Sharma, Iyad Ismail, Owais Kadwani, Sanchez Simpson, Catherine A. Read, Xiaohui Sun, Abdel Douiri, Y.C. Gary Lee, Liju Ahmed
Journal: European Respiratory Journal (2023)

Background The principal aim of malignant pleural effusion (MPE) management is to improve health-related quality of life (HRQoL) and symptoms. Methods In this open-label randomised controlled trial, patients with symptomatic MPE were randomly assigned to either indwelling pleural catheter (IPC) insertion with the option of talc pleurodesis or chest drain and talc pleurodesis. The primary end-point was global health status, measured with the 30-item European Organisation for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) at 30 days post-intervention. 142 participants were enrolled from July 2015 to December 2019. Results Of participants randomly assigned to the IPC (n=70) and chest drain (n=72) groups, primary outcome data were available in 58 and 56 patients, respectively. Global health status improved in both groups at day 30 compared with baseline: IPC (mean difference 13.11; p=0.001) and chest drain (mean difference 10.11; p=0.001). However, there was no significant between-group difference at day 30 (mean intergroup difference in baseline-adjusted global health status 2.06, 95% CI −5.86–9.99; p=0.61), day 60 or day 90. No significant differences were identified between groups in breathlessness and chest pain scores. All chest drain arm patients were admitted (median length of stay 4 days); seven patients in the IPC arm required intervention-related hospitalisation. Conclusions While HRQoL significantly improved in both groups, there were no differences in patient-reported global health status at 30 days. The outpatient pathway using an IPC was not superior to inpatient treatment with a chest drain.
Assessment of visual function in blind mice and monkeys with subretinally implanted nanowire arrays as artificial photoreceptors
Authors: Ruyi Yang, Peng Zhao, Liyang Wang, Chenli Feng, Chen Peng, Zhexuan Wang, Yingying Zhang, Minqian Shen, Kaiwen Shi, Shijun Weng, Chunqiong Dong, Fu Zeng, Tianyun Zhang, Xingdong Chen, Shuiyuan Wang, Yiheng Wang, Yuanyuan Luo, Qingyuan Chen, Yuqing Chen, Chengyong Jiang, Shanshan Jia, Zhaofei Yu, Jian Liu, Fei Wang, Su Jiang, Wendong Xu, Liang Li, Gang Wang, Xiaofen Mo, Gengfeng Zheng, Aihua Chen, Xingtao Zhou, Chunhui Jiang, Yuanzhi Yuan, Biao Yan, Jiayi Zhang
Journal: Nature Biomedical Engineering (2023)
High-throughput screening of genetic and cellular drivers of syncytium formation induced by the spike protein of SARS-CoV-2
Authors: Charles W. F. Chan, Bei Wang, Lang Nan, Xiner Huang, Tianjiao Mao, Hoi Yee Chu, Cuiting Luo, Hin Chu, Gigi C. G. Choi, Ho Cheung Shum, Alan S. L. Wong
Journal: Nature Biomedical Engineering (2023)

Abstract Mapping mutations and discovering cellular determinants that cause the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to induce infected cells to form syncytia would facilitate the development of strategies for blocking the formation of such cell–cell fusion. Here we describe high-throughput screening methods based on droplet microfluidics and the size-exclusion selection of syncytia, coupled with large-scale mutagenesis and genome-wide knockout screening via clustered regularly interspaced short palindromic repeats (CRISPR), for the large-scale identification of determinants of cell–cell fusion. We used the methods to perform deep mutational scans in spike-presenting cells to pinpoint mutable syncytium-enhancing substitutions in two regions of the spike protein (the fusion peptide proximal region and the furin-cleavage site). We also used a genome-wide CRISPR screen in cells expressing the receptor angiotensin-converting enzyme 2 to identify inhibitors of clathrin-mediated endocytosis that impede syncytium formation, which we validated in hamsters infected with SARS-CoV-2. Finding genetic and cellular determinants of the formation of syncytia may reveal insights into the physiological and pathological consequences of cell–cell fusion.
Rational immunosilencing of a promiscuous T-cell epitope in the capsid of an adeno-associated virus
Authors: So Jin Bing, Morten Seirup, Trish T. Hoang, Susana S. Najera, Collin Britten, Stephanee L. Warrington, Shiang-Ling Chu, Ronit Mazor
Journal: Nature Biomedical Engineering (2023)
Immune-privileged tissues formed from immunologically cloaked mouse embryonic stem cells survive long term in allogeneic hosts
Authors: Jeffrey Harding, Kristina Vintersten-Nagy, Huijuan Yang, Jean Kit Tang, Maria Shutova, Eric D. Jong, Ju Hee Lee, Mohammad Massumi, Tatiana Oussenko, Zohreh Izadifar, Puzheng Zhang, Ian M. Rogers, Michael B. Wheeler, Stephen J. Lye, Hoon-Ki Sung, ChengJin Li, Mohammad Izadifar, Andras Nagy
Journal: Nature Biomedical Engineering (2023)

Abstract The immunogenicity of transplanted allogeneic cells and tissues is a major hurdle to the advancement of cell therapies. Here we show that the overexpression of eight immunomodulatory transgenes ( Pdl1 , Cd200 , Cd47 , H2-M3 , Fasl , Serpinb9 , Ccl21 and Mfge8 ) in mouse embryonic stem cells (mESCs) is sufficient to immunologically ‘cloak’ the cells as well as tissues derived from them, allowing their survival for months in outbred and allogeneic inbred recipients. Overexpression of the human orthologues of these genes in human ESCs abolished the activation of allogeneic human peripheral blood mononuclear cells and their inflammatory responses. Moreover, by using the previously reported FailSafe transgene system, which transcriptionally links a gene essential for cell division with an inducible and cell-proliferation-dependent kill switch, we generated cloaked tissues from mESCs that served as immune-privileged subcutaneous sites that protected uncloaked allogeneic and xenogeneic cells from rejection in immune-competent hosts. The combination of cloaking and FailSafe technologies may allow for the generation of safe and allogeneically accepted cell lines and off-the-shelf cell products.
Anomalous peroxidase activity of cytochrome c is the primary pathogenic target in Barth syndrome
Authors: Valerian E. Kagan, Yulia Y. Tyurina, Karolina Mikulska-Ruminska, Deena Damschroder, Eduardo Vieira Neto, Alessia Lasorsa, Alexander A. Kapralov, Vladimir A. Tyurin, Andrew A. Amoscato, Svetlana N. Samovich, Austin B. Souryavong, Haider H. Dar, Abu Ramim, Zhuqing Liang, Pablo Lazcano, Jiajia Ji, Michael W. Schmidtke, Kirill Kiselyov, Aybike Korkmaz, Georgy K. Vladimirov, Margarita A. Artyukhova, Pushpa Rampratap, Laura K. Cole, Ammanamanchi Niyatie, Emma-Kate Baker, Jim Peterson, Grant M. Hatch, Jeffrey Atkinson, Jerry Vockley, Bernhard Kühn, Robert Wessells, Patrick C. A. van der Wel, Ivet Bahar, Hülya Bayir, Miriam L. Greenberg
Journal: Nature Metabolism (2023)
Cytokine-armed dendritic cell progenitors for antigen-agnostic cancer immunotherapy
Authors: Ali Ghasemi, Amaia Martinez-Usatorre, Luqing Li, Mehdi Hicham, Alan Guichard, Rachel Marcone, Nadine Fournier, Bruno Torchia, Darel Martinez Bedoya, Suzel Davanture, Mirian Fernández-Vaquero, Chaofan Fan, Jakob Janzen, Yahya Mohammadzadeh, Raphael Genolet, Nahal Mansouri, Mathias Wenes, Denis Migliorini, Mathias Heikenwalder, Michele De Palma
Journal: Nature Cancer (2023)

Abstract Dendritic cells (DCs) are antigen-presenting myeloid cells that regulate T cell activation, trafficking and function. Monocyte-derived DCs pulsed with tumor antigens have been tested extensively for therapeutic vaccination in cancer, with mixed clinical results. Here, we present a cell-therapy platform based on mouse or human DC progenitors (DCPs) engineered to produce two immunostimulatory cytokines, IL-12 and FLT3L. Cytokine-armed DCPs differentiated into conventional type-I DCs (cDC1) and suppressed tumor growth, including melanoma and autochthonous liver models, without the need for antigen loading or myeloablative host conditioning. Tumor response involved synergy between IL-12 and FLT3L and was associated with natural killer and T cell infiltration and activation, M1-like macrophage programming and ischemic tumor necrosis. Antitumor immunity was dependent on endogenous cDC1 expansion and interferon-γ signaling but did not require CD8 + T cell cytotoxicity. Cytokine-armed DCPs synergized effectively with anti-GD2 chimeric-antigen receptor (CAR) T cells in eradicating intracranial gliomas in mice, illustrating their potential in combination therapies.
Prevalence of chromosomal alterations in first-trimester spontaneous pregnancy loss
Authors: Rick Essers, Igor N. Lebedev, Ants Kurg, Elizaveta A. Fonova, Servi J. C. Stevens, Rebekka M. Koeck, Ulrike von Rango, Lloyd Brandts, Spyridon Panagiotis Deligiannis, Tatyana V. Nikitina, Elena A. Sazhenova, Ekaterina N. Tolmacheva, Anna A. Kashevarova, Dmitry A. Fedotov, Viktoria V. Demeneva, Daria I. Zhigalina, Gleb V. Drozdov, Salwan Al-Nasiry, Merryn V. E. Macville, Arthur van den Wijngaard, Jos Dreesen, Aimee Paulussen, Alexander Hoischen, Han G. Brunner, Andres Salumets, Masoud Zamani Esteki
Journal: Nature Medicine (2023)

Pregnancy loss is often caused by chromosomal abnormalities of the conceptus. The prevalence of these abnormalities and the allocation of (ab)normal cells in embryonic and placental lineages during intrauterine development remain elusive. In this study, we analyzed 1,745 spontaneous pregnancy losses and found that roughly half (50.4%) of the products of conception (POCs) were karyotypically abnormal, with maternal and paternal age independently contributing to the increased genomic aberration rate. We applied genome haplarithmisis to a subset of 94 pregnancy losses with normal parental and POC karyotypes. Genotyping of parental DNA as well as POC extra-embryonic mesoderm and chorionic villi DNA, representing embryonic and trophoblastic tissues, enabled characterization of the genomic landscape of both lineages. Of these pregnancy losses, 35.1% had chromosomal aberrations not previously detected by karyotyping, increasing the rate of aberrations of pregnancy losses to 67.8% by extrapolation. In contrast to viable pregnancies where mosaic chromosomal abnormalities are often restricted to chorionic villi, such as confined placental mosaicism, we found a higher degree of mosaic chromosomal imbalances in extra-embryonic mesoderm rather than chorionic villi. Our results stress the importance of scrutinizing the full allelic architecture of genomic abnormalities in pregnancy loss to improve clinical management and basic research of this devastating condition.
Robot-assisted abdominal surgery in children less than 5 months of age: retrospective cohort study
Authors: Yi Jin, Duote Cai, Shuhao Zhang, Wenjuan Luo, Yuebin Zhang, Zongwei Huang, Qingjiang Chen, Zhigang Gao
Journal: International Journal of Surgery (2023)

Background: Robot-assisted surgery is increasingly used in children. While robot-assisted surgery in children has been proved to be safe and feasible, use in infants is controversial. The purpose of this study was to present a study of robot-assisted abdominal surgery in children less than5 months of age. Materials and methods: A retrospective analysis of 111 patients less than 5 months of age who underwent abdominal surgery from April 2020 to December 2022 in our hospital. The data included clinical information, operative details, and postoperative outcomes. Results: Among these 111 patients, 67 underwent robot-assisted surgery and 44 underwent laparoscopic-assisted surgery, the robot-assisted group includes 40 patients with Hirschsprung disease, 20 patients with choledochal cysts, and 7 patients with intestinal duplication, the laparoscopic-assisted group includes 26 patients with Hirschsprung disease, 9 patients with choledochal cysts, and 9 patients with intestinal duplication. For Hirschsprung disease, the operation time was significantly longer ( P =0.013) and the intraoperative bleeding was significantly less ( P =0.000) in the robot-assisted group than the laparoscopic assisted group. For choledochal cysts, the median operation time of 180 mins for the robot-assisted group was not significantly longer than the laparoscopic assisted surgery group at 160 mins ( P =0.153). For intestinal duplication, the operation time was significantly longer ( P =0.002) in the robot-assisted group than the laparoscopic assisted group. For these three diseases, the hospitalization expense was significantly higher ( P &lt;0.05) in the robot-assisted group than the laparoscopic assisted group, there were no significant differences in complications, and postoperative fasting time between two groups ( P &gt;0.05). Conclusion: Robot-assisted abdominal surgery in children less than 5 months of age is safe and feasible. This study showed that the surgical indications for the Da Vinci robot system in children can be extended to infants.
A commentary on ‘Robotic-assisted total knee arthroplasty is more advantageous for knees with severe deformity: a randomized controlled trial study design’
Authors: Chenzhong Zong, Qingfu Wang, Gao Kuo, Xueqi Dong, Xiaoqing Zhang
Journal: International Journal of Surgery (2023)

Zong, Chenzhong; Wang, Qingfu; Kuo, Gao; Dong, Xueqi; Zhang, Xiaoqing Author Information
Surgery versus radiotherapy for limited-stage small cell esophageal carcinoma: a multicenter, retrospective, cohort study in China (ChiSCEC)
Authors: Jie Zhu, Yi Wang, Hongfu Sun, Yaowen Zhang, Wencheng Zhang, Wenbin Shen, Ning Yang, Bingxu Tan, Xiujun Su, Lei Li, Wei Dong, Jie Ma, Jian Zhang, Lina Zhao, Daqing Sun, Pei Yang, Lin Peng, Baosheng Li, Wei Huang, Qifeng Wang, Zhongxing Liao
Journal: International Journal of Surgery (2023)

Background: There is no standard management for small cell esophageal carcinoma (SCEC). The purpose of this multicenter, retrospective study (ChiSCER) was to investigate the treatment, outcomes, and risk factors impacting survival endpoints in patients with limited-stage SCEC (LS-SCEC). Materials and Methods: Consecutive patients with LS-SCEC from 14 institutions between 2000 and 2020 in China were enrolled. Survival curves were constructed using the Kaplan–Meier method and compared using a log-rank test. Univariate and multivariate Cox regression models and propensity score matching (PSM) analysis were adopted in the prognostic analysis. Results were reported as hazard ratio (HR), 95% confidence interval (CI), and P value. Statistical significance was set as P value &lt;0.05 in a two-tailed test. Results: Among 458 LS-SCEC patients, the median age was 63 [interquartile range (IQR), 57–68] years, and 318 (69%) were males. Eighty-four (18%), 167 (36%), and 207 (45%) patients received chemotherapy (CT) alone, CT plus definitive radiotherapy (CT+RT), and CT plus radical surgery (CT+S), respectively. With a median follow-up time of 58.7 (95% CI 48.9–68.6) months, the median overall survival (OS) and 3-year OS rate for all patients 24.3 (95% CI 21.6–27) months and 37.3% (95% CI 32.8–42.5%), respectively. Multivariate analysis indicated that treatment modes, Karnofsky performance status (KPS), TNM stage, and CT cycle were independent prognostic factors for OS ( P &lt;0.05). Compared with CT alone, patients treated with CT+RT (HR 0.57, 95% CI 0.41–0.8, P =0.001) or CT+S (HR 0.59, 95% CI 0.42–0.82, P =0.002) had an improved OS, with no significant survival differences between CT+S and CT+RT groups after multivariate and PSM analyses ( P &gt;0.05). Subgroup analysis indicated that compared with CT+RT, patients with tumor location at lower 1/3 (HR 0.59, 95% CI 0.37–0.93, P =0.03) or tumor length &gt;5 cm (HR 0.52, 95% CI 0.3–0.9, P =0.02) could obtain significant OS benefit from CT+S. Patients with tumor location at middle 1/3 (HR 1.55, 95% CI 1.03–2.36, P =0.04) or tumor length ≤5 cm (HR 1.49, 95% CI 1.02–2.17, P =0.04) favored CT+RT. Distant metastasis accounted for 73.7% of all treatment failures after multidisciplinary treatments. Conclusion: Surgery and RT were equally effective local therapies for patients with LS-SCEC. The personalized decision of local therapy should be made after comprehensive considerations on tumor location, length, comorbidities, and organ preservation.
Force-adjustable parallel-occlusion grasper
Authors: Hamza Khan, Stuart Coleman, Alfred Cuschieri
Journal: International Journal of Surgery (2023)

Background: During laparoscopic surgery, the operating surgeon grasps sections of the gastrointestinal tract (GIT), including delicate structures, with long (270 mm) 5 mm diameter graspers. These grasping instruments increase the risk of iatrogenic damage due to crushing of the grasped tissue. This risk is increased significantly by diseases such as bacterial peritonitis and inflammatory bowel disease and reduced but not abolished by using parallel-closing laparoscopic instruments. This study describes the design and laboratory testing of fully developed and tested smart graspers capable of reducing the grasping force used for inflamed tissues and hollow viscera. Materials and methods: In an ISO 13485-certified mechanical laboratory and CAD machine workshop, the authors have designed, developed, and evaluated a smart gasper capable of exerting a preselected uniform grasping force on the gastrointestinal tract and other structures/ tissues, through a mechanism incorporated in the handle of the instrument. This enables the control and graded reduction of the grasping force by the incorporation of a compression spring. The authors named the new instrument the force-adjustable parallel-occlusion grasper (FA-POG) because, in addition to applying a uniform force on the grasped bowel/tissue, it also enables the surgeon to select the force before grasping, depending on its physical condition, and pathological state. Results: FA-POG differs from traditional pinch-occlusion grasper in two respects: it exerts a uniform force on the grasped tissue/bowel and enables the operating surgeon to select and apply a predetermined uniform grasping force, ranging from 1 to 5 N, depending on the pathological condition of the bowel/structure. The ISO 13485-certified and fully developed prototype has been subjected to various grasping in-vitro tests using freshly harvested porcine small-bowel segments obtained from a local abattoir, using Instron tensiometry. Conclusions: The authors designed and α/β tested a parallel-occlusion gasper that enables the operating surgeon to select the force before grasping. This grasper design consists of end-effectors jaws with a 4-bar linkage mechanism for wide, uniform parallel-occlusion force, surpassing traditional scissor-type laparoscopic graspers. It incorporates a force-level controller knob, based on a spring-loaded mechanism, enabling surgeon-preselected grip force to prevent excessive grasping. The authors validated the design experimentally using porcine small-bowel segments, optimizing teeth for maximum grip friction to minimize slippage.
A brainstem circuit for phonation and volume control in mice
Authors: Avin Veerakumar, Joshua P. Head, Mark A. Krasnow
Journal: Nature Neuroscience (2023)

Abstract Mammalian vocalizations are critical for communication and are produced through the process of phonation, in which expiratory muscles force air through the tensed vocal folds of the larynx, which vibrate to produce sound. Despite the importance of phonation, the motor circuits in the brain that control it remain poorly understood. In this study, we identified a subpopulation of ~160 neuropeptide precursor Nts (neurotensin)-expressing neurons in the mouse brainstem nucleus retroambiguus (RAm) that are robustly activated during both neonatal isolation cries and adult social vocalizations. The activity of these neurons is necessary and sufficient for vocalization and bidirectionally controls sound volume. RAm Nts neurons project to all brainstem and spinal cord motor centers involved in phonation and activate laryngeal and expiratory muscles essential for phonation and volume control. Thus, RAm Nts neurons form the core of a brain circuit for making sound and controlling its volume, which are two foundations of vocal communication.